• Montserrat Batlle, Eulàlia Roig, Fèlix Perez-Villa, Sergio Lario, Pilar Cejudo-Martin, Ester García-Pras, José Ortiz, Mercé Roqué, Josefina Orús, Montserrat Rigol, Magdalena Heras, José Ramírez, and Wladimiro Jimenez.
• Experimental Cardiology Laboratory, Hospital Clínic de Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. mbatlle@clinic.ub.es
• J. Heart Lung Transplant. 2006 Sep 1; 25 (9): 1117-25.

BackgroundThe activation of the renin-angiotensin system (RAS) contributes to the progression of left ventricular dysfunction. A novel human homologue of the angiotensin-converting enzyme (ACE), named ACE2, has been described but its role in human heart failure (HF) has not been elucidated. Besides, there is controversy as to whether the major angiotensin II-forming-activity in heart is ACE or chymase released from mast cells. Furthermore, long-term blockade of nitric oxide (NO) synthesis has been shown to increase ACE activity. To assess the locally activated vasoactive mediators that may contribute to the ventricular deterioration process, we sought to simultaneously analyze their expression in failing hearts.MethodsWe analyzed left ventricular biopsies from 30 patients with heart failure undergoing heart transplantation and 12 organ donors. The mRNA levels of ACE, ACE2, chymase and endothelial nitric oxide synthase (eNOS), were quantified by real-time polymerase chain reaction and mast cell density was assessed by immunohistochemistry. The mRNA levels of the atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP) were also quantified as controls.ResultsThere was higher ACE and chymase mRNA expression and mast cell density in failing than in control myocardium and no changes in ACE2 expression were detected. eNOS mRNA levels were lower in failing hearts. Both ANP and BNP expression were higher in pathological than in control samples.ConclusionsThese data document a decompensation of vasoactive systems that may contribute to the progressive impairment of the myocardial function in HF. On the other hand, ACE2 mRNA expression is not altered in human end-stage HF.

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